Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Sci. Signal., 18 January 2011
Vol. 4, Issue 156, p. ra2
[DOI: 10.1126/scisignal.2001211]

RESEARCH ARTICLES

The Kinase SGK1 in the Endoderm and Mesoderm Promotes Ectodermal Survival by Down-Regulating Components of the Death-Inducing Signaling Complex

Tatsuya Endo1, Morioh Kusakabe1,2*, Kazunori Sunadome1, Takuya Yamamoto1, and Eisuke Nishida1,2*

1 Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan.
2 Japan Science and Technology–Core Research for Evolutional Science and Technology, Chiyoda-ku, Tokyo 102-0075, Japan.

Abstract: A balance between cell survival and apoptosis is essential for animal development. Although proper development involves multiple interactions between germ layers, little is known about the intercellular and intertissue signaling pathways that promote cell survival in neighboring or distant germ layers. We found that serum- and glucocorticoid-inducible kinase 1 (SGK1) promoted ectodermal cell survival during early Xenopus embryogenesis through a non–cell-autonomous mechanism. Dorsal depletion of SGK1 in Xenopus embryos resulted in shortened axes and reduced head structures with defective eyes, and ventral depletion led to defective tail morphologies. Although the gene encoding SGK1 was mainly expressed in the endoderm and dorsal mesoderm, knockdown of SGK1 caused excessive apoptosis in the ectoderm. SGK1-depleted ectodermal explants showed little or no apoptosis, suggesting non–cell-autonomous effects of SGK1 on ectodermal cells. Microarray analysis revealed that SGK1 knockdown increased the expression of genes encoding FADD (Fas-associated death domain protein) and caspase-10, components of the death-inducing signaling complex (DISC). Inhibition of DISC function suppressed excessive apoptosis in SGK1-knockdown embryos. SGK1 acted through the transcription factor nuclear factor {kappa}B (NF-{kappa}B) to stimulate production of bone morphogenetic protein 7 (BMP7), and overexpression of BMP7 in SGK1-knockdown embryos reduced the abundance of DISC components. We show that phosphoinositide 3-kinase (PI3K) functioned upstream of SGK1, thus revealing an endodermal and mesodermal pathway from PI3K to SGK1 to NF-{kappa}B that produces BMP7, which promotes ectodermal survival by decreasing DISC function.

* To whom correspondence should be addressed. E-mail: morioh{at}lif.kyoto-u.ac.jp (M.K.); nishida{at}lif.kyoto-u.ac.jp (E.N.)

Citation: T. Endo, M. Kusakabe, K. Sunadome, T. Yamamoto, E. Nishida, The Kinase SGK1 in the Endoderm and Mesoderm Promotes Ectodermal Survival by Down-Regulating Components of the Death-Inducing Signaling Complex. Sci. Signal. 4, ra2 (2011).

Read the Full Text

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
The serum- and glucocorticoid-inducible kinase 1 (SGK1) influences platelet calcium signaling and function by regulation of Orai1 expression in megakaryocytes.
O. Borst, E.-M. Schmidt, P. Munzer, T. Schonberger, S. T. Towhid, M. Elvers, C. Leibrock, E. Schmid, A. Eylenstein, D. Kuhl, et al. (2012)
Blood 119, 251-261
   Abstract »    Full Text »    PDF »
Oncogenic EGFR Signaling Activates an mTORC2-NF-{kappa}B Pathway That Promotes Chemotherapy Resistance.
K. Tanaka, I. Babic, D. Nathanson, D. Akhavan, D. Guo, B. Gini, J. Dang, S. Zhu, H. Yang, J. De Jesus, et al. (2011)
Cancer Discovery 1, 524-538
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882